Our approach to the problem of developing effective trypanocidal drugs is to study two specific and related areas of the biochemistry of trypanosomes. We are concerned with the regulation and control of the functioning of the electron transport system during the life cycle of trypanosomes. In order to identify targets for potential trypanocides, we must learn more about the properties of the mitochondrion in trypanosomes. Our specific aims for the period of the proposal are: 1. To determine whether kinetoplast DNA is transcribed in bloodstream and culture forms of T. brucei; 2. To study the presence and function of the RNA polymerases in the mitochondrion and nucleus of T. brucei; 3. To characterize the effect of trypanocidal drugs on the macromolecular synthesis and function of the electron transport system in T. brucei; 4. To study the purification and properties of the unique alpha-GP oxidase system; 5. To characterize what are the sequence of events during the synthesis of the electron transport system during the differentiation of T. brucei bloodstream, stumpy trypomastigotes to culture, procyclic trypomastigotes; 6. To try to identify the factors regulating the repression or initiation of the electron transport system during the life cycle of T. brucei.